Phenotypes associated with this allele

• Allele Symbol: Smn1^tm1Msd
• Allele Name: targeted mutation 1, Michael Sendtner
• Allele ID: MGI:2183946
• Summary: 51 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Smn1^tm1Msd/Smn1^tm1Msd	involves: 129P2/OlaHsd * MF1	MGI:2675312
ht2	Smn1^tm1Msd/Smn1^tm1Rako	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:4398737
ht3	Smn1^tm1Msd/Smn1^tm1.1Dscd	involves: 129S/SvEv * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6	MGI:4836986
cn4	Olig2^tm1(cre)Tmj/Olig2^+ Smn1^tm1Jme/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^+	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5289776
cn5	Olig2^tm1(cre)Tmj/Olig2^+ Smn1^tm1Jme/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129 * 129P2/OlaHsd * FVB/N	MGI:5289775
cx6	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^+	B6.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd	MGI:3785817
cx7	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	B6.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd	MGI:3785816
cx8	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)11Tro/0	B6.Cg-Smn1^tm1Msd Tg(SMN2)11Tro	MGI:3832212
cx9	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)11Tro/Tg(SMN2)11Tro	B6.Cg-Smn1^tm1Msd Tg(SMN2)11Tro	MGI:3832209
cx10	Smn1^tm1Msd/Smn1^+ Tg(SMN2)11Tro/Tg(SMN2)11Tro	B6.Cg-Smn1^tm1Msd Tg(SMN2)11Tro	MGI:3832214
cx11	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)46Tro/0	B6.Cg-Smn1^tm1Msd Tg(SMN2)46Tro	MGI:3832211
cx12	Smn1^tm1Msd/Smn1^+ Tg(SMN2)46Tro/Tg(SMN2)46Tro	B6.Cg-Smn1^tm1Msd Tg(SMN2)46Tro	MGI:3832213
cx13	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)46Tro/Tg(SMN2)46Tro	B6.Cg-Smn1^tm1Msd Tg(SMN2)46Tro	MGI:3832210
cx14	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)11Tro/0	B6.Cg-Tg(SMN2)11Tro Smn1^tm1Msd/J	MGI:4818921
cx15	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)11Tro/Tg(SMN2)11Tro	B6.Cg-Tg(SMN2)11Tro Smn1^tm1Msd/J	MGI:4818922
cx16	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)11Tro/0 Tg(SMN2)46Tro/0	B6.Cg-Tg(SMN2)11Tro Tg(SMN2)46Tro Smn1^tm1Msd/J	MGI:4818925
cx17	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)46Tro/0	B6.Cg-Tg(SMN2)46Tro Smn1^tm1Msd/J	MGI:4818924
cx18	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)46Tro/Tg(SMN2)46Tro	B6.Cg-Tg(SMN2)46Tro Smn1^tm1Msd/J	MGI:4818923
cx19	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	FVB.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd/J	MGI:3785611
cx20	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^+ Tg(SMN2*delta7)4299Ahmb/0	FVB.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb	MGI:3785824
cx21	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb	FVB.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb	MGI:3785825
cx22	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/0	FVB.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb/J	MGI:5490996
cx23	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb	FVB.Cg-Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb/J	MGI:3785610
cx24	Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Smn1^tm1Msd/Smn1^tm1Msd	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6J * FVB/N	MGI:6117364
cx25	Pfn2^tm1Wit/Pfn2^tm1Wit Smn1^tm1Msd/Smn1^tm1Rako	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:4398738
cx26	Pfn2^tm1Wit/Pfn2^+ Smn1^tm1Msd/Smn1^tm1Rako	involves: 129P2/OlaHsd * C57BL/6 * CD-1	MGI:4398739
cx27	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1-SMN2*)16Cll/0 Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:5490787
cx28	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/?	involves: 129P2/OlaHsd * C57BL/6J * FVB	MGI:2677019
cx29	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2)566Ahmb/?	involves: 129P2/OlaHsd * C57BL/6J * FVB	MGI:2677023
cx30	Gemin2^tm1Msd/Gemin2^+ Smn1^tm1Msd/Smn1^+	involves: 129P2/OlaHsd * C57BL/6 * MF1	MGI:2451057
cx31	Smn1^tm1Msd/Smn1^tm1Msd Tg(ACTA1-SMN)63Ahmb/Tg(ACTA1-SMN)63Ahmb Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:3775248
cx32	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*A111G)591Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847441
cx33	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2*A111G)588Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847443
cx34	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*)1951Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847444
cx35	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1*A2G)2023Ahmb/0 Tg(SMN2*A111G)591Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847565
cx36	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1*A2G)2023Ahmb/0 Tg(SMN2*A111G)588Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847566
cx37	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^+ Tg(SMN2*A111G)591Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847439
cx38	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN2*A111G)591Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847438
cx39	Smn1^tm1Msd/Smn1^tm1Msd Tg(ACTA1-SMN)69Ahmb/Tg(ACTA1-SMN)69Ahmb Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:3775240
cx40	Smn1^tm1Msd/Smn1^tm1Msd Tg(Prnp-SMN)92Ahmb/0 Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:3775226
cx41	Smn1^tm1Msd/Smn1^tm1Msd Tg(Prnp-SMN)92Ahmb/Tg(Prnp-SMN)92Ahmb Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:3775225
cx42	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1*A2G)2023Ahmb/?	involves: 129P2/OlaHsd * FVB/N	MGI:3663317
cx43	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1*A2G)2023Ahmb/Tg(SMN1*A2G)2023Ahmb Grm7^Tg(SMN2)89Ahmb/?	involves: 129P2/OlaHsd * FVB/N	MGI:3663316
cx44	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:4835060
cx45	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:4835061
cx46	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb Tg(SMN2*A111G)588Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847440
cx47	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1*A2G)2023Ahmb/0 Grm7^Tg(SMN2)89Ahmb/Grm7^+	involves: 129P2/OlaHsd * FVB/N	MGI:3663312
cx48	Smn1^tm1Msd/Smn1^tm1Msd Grm7^Tg(SMN2)89Ahmb/Grm7^+ Tg(SMN2*A111G)588Ahmb/0	involves: 129P2/OlaHsd * FVB/N	MGI:3847437
cx49	Smn1^tm1Msd/Smn1^tm1Msd Tg(SMN1*A2G)2023Ahmb/0 Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:3775243
cx50	Smn1^tm1Msd/Smn1^tm1Msd Tg(ACTA1-SMN)63Ahmb/0 Grm7^Tg(SMN2)89Ahmb/Grm7^Tg(SMN2)89Ahmb	involves: 129P2/OlaHsd * FVB/N	MGI:3775247
cx51	Gt(ROSA)26Sor^tm1.1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^tm1.1(rtTA,EGFP)Nagy Smn1^tm1Msd/Smn1^+ Tg(SMN2)#Ahmb/Tg(SMN2)#Ahmb Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb Tg(tetO-SMN2,-luc)#aAhmb/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB	MGI:5286604

Genotype
MGI:2675312

hm1

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd
• Genetic Background: involves: 129P2/OlaHsd * MF1

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

embryonic lethality before implantation, complete penetrance ( J:42813 )

• massive cell death during early development

cellular

abnormal apoptosis ( J:42813 )

• increased apoptotic cell death at 90 to 100 hours post coitum, relative to wild-type and heterozygous embryos

embryo

embryonic growth retardation ( J:42813 )

• the spherical shape embryos was lost and they appeared shrunken

abnormal embryonic tissue morphology ( J:42813 )

• aberrant development 80 hours post coitum

absent blastocoele ( J:42813 )

• although morula compaction proceeded in most embryos, a blastocoel cavity failed to form and the spherical shape was lost

growth/size/body

embryonic growth retardation ( J:42813 )

• the spherical shape embryos was lost and they appeared shrunken

Genotype
MGI:4398737

ht2

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Rako
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

premature death ( J:154248 )

• most mice die by 1 month of age

nervous system

decreased motor neuron number ( J:154248 )

• in the brain stem and spinal cord at P21

skeleton

abnormal spine curvature ( J:154248 )

• in mice that survive beyond 1 month

behavior/neurological

abnormal gait ( J:154248 )

• in mice that survive beyond 1 month

paraparesis ( J:154248 )

• mice that survive beyond 1 month exhibit hind limb weakness

growth/size/body

decreased body size ( J:154248 )

• at 3 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:154248

Genotype
MGI:4836986

ht3

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1.1Dscd
• Genetic Background: involves: 129S/SvEv * 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/6

behavior/neurological

decreased grip strength ( J:164889 )

decreased vertical activity ( J:164889 )

• at 60 days

decreased locomotor activity ( J:164889 )

• at 60 days

nervous system

nervous system phenotype ( J:164889 )

N • mice exhibit normal neuromuscular junctions morphology and neuromuscular transmissions

Genotype
MGI:5289776

cn4

• Allelic Composition: Olig2^tm1(cre)Tmj/Olig2⁺; Smn1^tm1Jme/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: involves: 129 * 129P2/OlaHsd * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:164292 )

• die by P2

Genotype
MGI:5289775

cn5

• Allelic Composition: Olig2^tm1(cre)Tmj/Olig2⁺; Smn1^tm1Jme/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129 * 129P2/OlaHsd * FVB/N

mortality/aging

decreased survivor rate ( J:164292 )

• about 70% of mutants survive to about 12 months of age

premature death ( J:164292 )

• about 30% of mutants die before 12 months of age

growth/size/body

decreased body weight ( J:164292 )

• by the second day after birth, mutants show a 15% decrease in weight compared to controls

behavior/neurological

decreased grip strength ( J:164292 )

• mutants exhibit reduced grip strength, indicating weakness

muscle

abnormal muscle morphology ( J:164292 )

• reduced muscle mass

increased skeletal muscle fiber size ( J:164292 )

• average size of mutant fibers is larger than controls

decreased skeletal muscle fiber number ( J:164292 )

skeletal muscle fiber degeneration ( J:164292 )

• muscle fiber loss occurs after P7

muscular atrophy ( J:164292 )

• atrophic fibers are seen in proximal (triceps) and distal (gastrocnemius) muscles

• small but significant proportion of muscle fibers exhibit centrally located nuclei, suggesting an ongoing regenerative process in muscle

muscle weakness ( J:164292 )

• in an impaired righting ability test, mutants are noticeably weaker by postnatal day 2

• impaired righting reflex gradually subsides so that by the end of the second week of life, differences between mutants and controls are no longer seen

• however mutants continue to display weakness as adults

nervous system

abnormal sensory neuron innervation pattern ( J:164292 )

• neonates exhibit a reduction of vGlut1 bouton numbers and their areas on motor neurons and a reduction of the total numbers of puncta in the ventral horn, indicating an aberration in the projection of proprioceptive sensory neurons onto ventral horns

motor neuron degeneration ( J:164292 )

• by P40, mutants exhibit an approximate 40% and 25% reduction in cervical and lumbar motor neurons, respectively

abnormal synaptic bouton morphology ( J:164292 )

• the number of boutons juxtaposed against ChAT-positive motor neurons is reduced

• mean area of these synaptic boutons is reduced, suggesting an alteration in the synaptic coverage of the ventral horn motor neurons by Ia sensory terminals

• at the presynapse, neurofilament aggregates infiltrate nerve terminals and terminal arbors are swollen

• abnormal amounts of neurofilament protein persist in the nerve terminals of both proximal and distal muscles

• abnormal localization of synaptic vesicles in mutant terminals at P8 but no longer visible at P12

abnormal neuromuscular synapse morphology ( J:164292 )

• NMJs in the triceps muscle are smaller, misshapen, and less mature than in controls or in mutant gastrocnemius muscle, indicating delayed maturation

• fragmented NMJs are seen in both triceps and gastrocnemius muscles

• at the postsynapse, more than 75% of gastrocnemial acetylcholine receptor clusters attain the normal pretzel-like conformation, but more than half of them appear fragmented and are measurably larger than in control NMJs

• acetylcholine receptor clusters of the triceps fail to attain the level of complexity as gastrocnemial muscle

abnormal synaptic transmission ( J:164292 )

• mutants exhibit severe defects of neuromuscular transmission at P8 but these defects are attenuated by P12 as disease progresses

• at P8, 100 Hz nerve stimulation of muscle is only able to produce 34% of the tension produced by direct muscle stimulation compared to 72% in controls, indicating that many junctions fail to active muscle fibers to threshold[?]

• at 100 Hz asynchronous release of calcium disappears at mutant NMJs undergoing numerous failures, suggesting there is little calcium entry into the nerve terminals during these events

• at P8, a decrease in the mean quantal content of the mutant junctions compared with controls, but at P10 and P12 mutant NJMs, the quantal content increases to control levels

abnormal CNS synaptic transmission ( J:164292 )

abnormal PNS synaptic transmission ( J:164292 )

abnormal miniature endplate potential ( J:164292 )

• mean mEPP amplitude at mutant NMJs is 50-100% greater than at control junctions at P8, P10 and P12

• semitendinosus muscle of 3 month old mutants shows an increase in mEPP amplitude despite a decrease in input resistance, indicating that neuromuscular transmission defects persist at the NMJs of adults

skeleton

kyphosis ( J:164292 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:164292

Genotype
MGI:3785817

cx6

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: B6.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd

mortality/aging

postnatal lethality, complete penetrance ( J:97103 )

• mice do not survive past 2 days with a mean survival of 1 day

Genotype
MGI:3785816

cx7

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: B6.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd

mortality/aging

lethality, complete penetrance ( J:256720 )

• Background Sensitivity: double homozygotes are not found postnatally unlike when mice are on an inbred FVB/NJ background

postnatal lethality, complete penetrance ( J:97103 )

• mice do not survive past 8 days with a mean survival of 5 days

growth/size/body

decreased body weight ( J:97103 )

• at P5

Genotype
MGI:3832212

cx8

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)11Tro/0
• Genetic Background: B6.Cg-Smn1^tm1Msd Tg(SMN2)11Tro

mortality/aging

embryonic lethality ( J:144852 )

Genotype
MGI:3832209

cx9

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)11Tro/Tg(SMN2)11Tro
• Genetic Background: B6.Cg-Smn1^tm1Msd Tg(SMN2)11Tro

mortality/aging

neonatal lethality, incomplete penetrance ( J:144852 )

postnatal lethality, complete penetrance ( J:144852 )

growth/size/body

decreased birth body size ( J:144852 )

• mice that die at or soon after birth are slightly smaller than normal littermates

decreased body weight ( J:144852 )

• mice surviving beyond the neonatal period appear normal compared to normal littermates, but after 48 hours exhibit diminished weight gain

abnormal embryonic growth/weight/body size ( J:144852 )

• mice that die at or soon after birth are slightly smaller than normal littermates

Genotype
MGI:3832214

cx10

• Allelic Composition: Smn1^tm1Msd/Smn1⁺; Tg(SMN2)11Tro/Tg(SMN2)11Tro
• Genetic Background: B6.Cg-Smn1^tm1Msd Tg(SMN2)11Tro

nervous system

nervous system phenotype ( J:144852 )

N • homozygous mice do not show an spinal muscular atrophy (SMA)-like phenotype

Genotype
MGI:3832211

cx11

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)46Tro/0
• Genetic Background: B6.Cg-Smn1^tm1Msd Tg(SMN2)46Tro

mortality/aging

embryonic lethality ( J:144853 )

Genotype
MGI:3832213

cx12

• Allelic Composition: Smn1^tm1Msd/Smn1⁺; Tg(SMN2)46Tro/Tg(SMN2)46Tro
• Genetic Background: B6.Cg-Smn1^tm1Msd Tg(SMN2)46Tro

nervous system

nervous system phenotype ( J:144853 )

N

Genotype
MGI:3832210

cx13

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)46Tro/Tg(SMN2)46Tro
• Genetic Background: B6.Cg-Smn1^tm1Msd Tg(SMN2)46Tro

craniofacial

abnormal tooth morphology ( J:144853 )

• some animals have necrotic lesions on the teeth

integument

skin lesions ( J:144853 )

• homozygous mice exhibit necrotic lesions on their tails and ears

growth/size/body

abnormal tooth morphology ( J:144853 )

• some animals have necrotic lesions on the teeth

skeleton

abnormal tooth morphology ( J:144853 )

• some animals have necrotic lesions on the teeth

Genotype
MGI:4818921

cx14

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)11Tro/0
• Genetic Background: B6.Cg-Tg(SMN2)11Tro Smn1^tm1Msd/J

mortality/aging

embryonic lethality ( J:159930 )

Genotype
MGI:4818922

cx15

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)11Tro/Tg(SMN2)11Tro
• Genetic Background: B6.Cg-Tg(SMN2)11Tro Smn1^tm1Msd/J

mortality/aging

postnatal lethality, complete penetrance ( J:159930 )

• mice die 6 days after birth

growth/size/body

weight loss ( J:159930 )

• mice start to lose weight 48 hours after birth unlike wild-type mice

Genotype
MGI:4818925

cx16

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)11Tro/0; Tg(SMN2)46Tro/0
• Genetic Background: B6.Cg-Tg(SMN2)11Tro Tg(SMN2)46Tro Smn1^tm1Msd/J

mortality/aging

decreased survivor rate ( J:159930 )

• more mice survive to adulthood and exhibit normal lethality when Tg(SMN2)11Tro is inherited paternally and Tg(SMN2)46Tro maternally than the reverse

postnatal lethality, incomplete penetrance ( J:159930 )

• average survival is 15 days when Tg(SMN2)11Tro is inherited maternally and Tg(SMN2)46Tro paternally

• median survival is 14 days when Tg(SMN2)11Tro is inherited maternally and Tg(SMN2)46Tro paternally

• median survival is 22 days when Tg(SMN2)11Tro is inherited paternally and Tg(SMN2)46Tro maternally

nervous system

decreased motor neuron number ( J:159930 )

• at P15, mice exhibit a decrease in motor neurons in the lumbar vertebrae compared to in wild-type mice

abnormal synaptic bouton morphology ( J:159930 )

• synpatic boutons exhibit neurofilament accumulation, are thick and swollen, and contain axonal disorganization compared to in wild-type mice

abnormal neuromuscular synapse morphology ( J:159930 )

• at P15, neuromuscular synapses are disorganized with loss of endplate architecture compared to in wild-type mice

abnormal phrenic nerve morphology ( J:159930 )

• at P15, mice exhibit a non-statistically significant axon loss in the phrenic nerves unlike wild-type mice

abnormal sciatic nerve morphology ( J:159930 )

• at P15, mice exhibit a reduction in the number of myelinated axons of the ventral roots of the sciatic nerve compared with wild-type mice

axon degeneration ( J:159930 )

• at P15, mice exhibit a reduction in the number of myelinated axons of the ventral roots of the sciatic nerve compared with wild-type mice

• at P15, mice exhibit a non-statistically significant axon loss in the phrenic nerves unlike wild-type mice

muscle

abnormal skeletal muscle fiber morphology ( J:159930 )

• muscle fiber diameter in the gastrocnemius is reduced compared to in wild-type mice

muscular atrophy ( J:159930 )

abnormal muscle electrophysiology ( J:159930 )

• at P15, mice exhibit reduced compound muscle action potential (CMAP) amplitude and extend CMAP latency and duration compared with wild-type mice

progressive muscle weakness ( J:159930 )

• at P9 and worsening over the following week

respiratory system

abnormal respiration ( J:159930 )

• from P1 to P7, maturation of breathing variables is impaired compared with wild-type mice

apnea ( J:159930 )

• at P7, mice exhibit apneas unlike wild-type mice

abnormal respiratory mechanics ( J:159930 )

• at P7, breath duration is increased compared to in wild-type mice

• however, breath duration at P1 is normal

decreased pulmonary ventilation ( J:159930 )

• at P7 but not P1, mice exhibit decreased pulmonary ventilation compared with wild-type mice

• however, mice exhibit a normal increase in ventilation in response to hypoxia

behavior/neurological

behavior/neurological phenotype ( J:159930 )

N • mice exhibit normal righting response

N • mice exhibit normal response to hypoxia including normal increase in ventilation, ultrasonic vocalization, and motor responses

abnormal gait ( J:159930 )

• at P14

positive geotaxis ( J:159930 )

• mice exhibit reduced performance in a negative geotaxis test compared with wild-type mice

• up to P12, mice fail to reorient themselves gravitationally head upwards within 60 seconds or exhibit increased latency compared with wild-type mice

increased thermal nociceptive threshold ( J:159930 )

limbs/digits/tail

abnormal autopod morphology ( J:159930 )

• in mice that survive to adulthood

abnormal tail morphology ( J:159930 )

• in mice that survive to adulthood

growth/size/body

abnormal outer ear morphology ( J:159930 )

• in mice that survive to adulthood

slow postnatal weight gain ( J:159930 )

• after P4

hearing/vestibular/ear

abnormal outer ear morphology ( J:159930 )

• in mice that survive to adulthood

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:159930 )

N • mice exhibit normal response to hypoxia including normal increase in ventilation, ultrasonic vocalization, and motor responses

craniofacial

abnormal outer ear morphology ( J:159930 )

• in mice that survive to adulthood

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:159930

Genotype
MGI:4818924

cx17

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)46Tro/0
• Genetic Background: B6.Cg-Tg(SMN2)46Tro Smn1^tm1Msd/J

mortality/aging

embryonic lethality ( J:159930 )

Genotype
MGI:4818923

cx18

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)46Tro/Tg(SMN2)46Tro
• Genetic Background: B6.Cg-Tg(SMN2)46Tro Smn1^tm1Msd/J

mortality/aging

mortality/aging ( J:159930 )

N • mice exhibit a normal lifespan

limbs/digits/tail

abnormal autopod morphology ( J:159930 )

• mice exhibit swollen hind paws unlike wild-type mice

abnormal tail morphology ( J:159930 )

• mice exhibit shortening and loss of their tails unlike wild-type mice

hearing/vestibular/ear

abnormal outer ear morphology ( J:159930 )

• mice exhibit degeneration of the external ear tissue unlike in wild-type mice

growth/size/body

abnormal outer ear morphology ( J:159930 )

• mice exhibit degeneration of the external ear tissue unlike in wild-type mice

slow postnatal weight gain ( J:159930 )

craniofacial

abnormal outer ear morphology ( J:159930 )

• mice exhibit degeneration of the external ear tissue unlike in wild-type mice

Genotype
MGI:3785611

cx19

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd/J

mortality/aging

mortality/aging ( J:256720 )

N • Background Sensitivity: double homozygotes are detected postnatally unlike when mice are on an inbred C57BL/6J background or on a mixed background involving predominantly 129 and C57BL/6J

postnatal lethality ( J:194969 )

• mean lifespan is 7 days

nervous system

abnormal innervation pattern to muscle ( J:132467 )

• mice preferentially lack innervation of the caudal band of the levator auris longus

abnormal neuromuscular synapse morphology ( J:132467 )

• many endplates are partially occupied or vacant unlike in wild-type mice

muscle

decreased skeletal muscle fiber diameter ( J:132467 )

• muscle fiber diameter is decreased in both slow- and fast-twitch muscles compared to in wild-type mice

growth/size/body

decreased body weight ( J:194969 )

Genotype
MGI:3785824

cx20

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺; Tg(SMN2*delta7)4299Ahmb/0
• Genetic Background: FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb

mortality/aging

postnatal lethality, complete penetrance ( J:97103 )

• mice do not survive past 16 days with a mean survival of 10 days

Genotype
MGI:3785825

cx21

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb
• Genetic Background: FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb

mortality/aging

postnatal lethality, complete penetrance ( J:97103 )

• mice do not survive past 17 days with a mean survival of 13 days

behavior/neurological

impaired righting response ( J:97103 )

• at P5

impaired balance ( J:97103 )

• by day 10, mice experience difficulty walking and often fall while walking unlike wild-type mice

impaired limb coordination ( J:97103 )

• by day 10, mice experience difficulty walking and often fall while walking unlike wild-type mice

abnormal gait ( J:97103 )

• at P10, mice exhibit abnormal gait with fibrillation of the hindlimbs

nervous system

decreased motor neuron number ( J:97103 )

• in the lumbar region of the spinal cord at P9

• however, spinal motor neuron numbers at P4 are normal

abnormal neuromuscular synapse morphology ( J:97103 )

• at P14, many neuromuscular junctions are partially innervated or not innervated

• the diameter of neuromuscular junctions is smaller than in wild-type mice

muscle

skeletal muscle fiber atrophy ( J:97103 )

• at P14, muscle fibers of the gastrocnemius are small due to atrophy

growth/size/body

decreased body weight ( J:97103 )

• at P5

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:97103

Genotype
MGI:5490996

cx22

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*delta7)4299Ahmb/0
• Genetic Background: FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb/J

mortality/aging

postnatal lethality ( J:194969 )

• mean lifespan is 13 days

growth/size/body

decreased body weight ( J:194969 )

cardiovascular system

thin interventricular septum ( J:194969 )

cardiac interstitial fibrosis ( J:194969 )

• mutants exhibit an increase in cardiac fibrosis compared to unaffected wild-type controls

muscle

decreased skeletal muscle fiber size ( J:194969 )

cellular

cardiac interstitial fibrosis ( J:194969 )

• mutants exhibit an increase in cardiac fibrosis compared to unaffected wild-type controls

Genotype
MGI:3785610

cx23

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb
• Genetic Background: FVB.Cg-Grm7^{Tg(SMN2)89Ahmb} Smn1^tm1Msd Tg(SMN2*delta7)4299Ahmb/J

mortality/aging

postnatal lethality, complete penetrance ( J:164446 )

• average survival of about 2 weeks

nervous system

abnormal sympathetic system morphology ( J:164446 )

• TH staining of the heart to visualize sympathetic innervation indicates that mutants exhibit fewer major neuronal branches and they appear thinner and less distinct

abnormal innervation pattern to muscle ( J:132467 )

• mice preferentially lack innervation of the caudal band of the levator auris longus

abnormal neuromuscular synapse morphology ( J:132467 )

• many endplates are partially occupied or vacant unlike in wild-type mice

• mice exhibit both post- and pre-synaptic pathology at motor neuron endplates

muscle

dilated cardiomyopathy ( J:164446 )

decreased skeletal muscle fiber diameter ( J:132467 )

• muscle fiber diameter is decreased in both slow- and fast-twitch muscles compared to in wild-type mice

cardiovascular system

abnormal heart morphology ( J:164446 )

• hearts appear flaccid and lack defined shape and gross attenuation of walls at P10 and P13

dilated cardiomyopathy ( J:164446 )

abnormal blood flow velocity ( J:164446 )

• echocardiography indicates that P6 mice exhibit deficiencies in blood flow out of the right ventricle at the pulmonary valve, with decreased peak velocity and peak gradient, indicating a reduction in pumping efficiency and blood flow from the right ventricle to the lungs

increased heart rate variability ( J:164446 )

• as mice near end of life, they display a large increase in heart rate variability, ultimately displaying adjacent RR intervals that are highly inconsistent

decreased heart rate ( J:164446 )

• mice present bradycardia as early as 2 days of age, before neuromuscular symptoms

• bradyarrhythmia is characterized by progressive heart block and reduced ventricular depolarization efficiency

prolonged PR interval ( J:164446 )

• at P4, mice have a first-degree heart block characterized by elongated PR interval durations

• at P10, sharp increase in the PR interval and breakdown of cardiac rhythm as mutants exhibit progressive heart block

prolonged QRS complex duration ( J:164446 )

• elongation of the time of ventricular depolarization through an increase in QRS interval duration beginning at P4

growth/size/body

decreased body size ( J:164446 )

weight loss ( J:164446 )

• begin to lose weight at around P10

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:164446

Genotype
MGI:6117364

cx24

• Allelic Composition: Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Smn1^tm1Msd/Smn1^tm1Msd
• Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6J * FVB/N

mortality/aging

lethality, complete penetrance ( J:256720 )

• Background Sensitivity: double homozygotes are not found postnatally unlike when mice are on an inbred FVB/NJ background

Genotype
MGI:4398738

cx25

• Allelic Composition: Pfn2^tm1Wit/Pfn2^tm1Wit; Smn1^tm1Msd/Smn1^tm1Rako
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

premature death ( J:154248 )

• most mice die by 1 month of age

growth/size/body

decreased body size ( J:154248 )

• at 3 weeks of age

Genotype
MGI:4398739

cx26

• Allelic Composition: Pfn2^tm1Wit/Pfn2⁺; Smn1^tm1Msd/Smn1^tm1Rako
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CD-1

mortality/aging

premature death ( J:154248 )

• most mice die by 1 month of age

nervous system

decreased motor neuron number ( J:154248 )

• in the brain stem and spinal cord at 3 weeks of age

growth/size/body

decreased body size ( J:154248 )

• at 3 weeks of age

weight loss ( J:154248 )

Genotype
MGI:5490787

cx27

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1-SMN2*)16Cll/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * FVB/N

mortality/aging

premature death ( J:194969 )

• mean lifespan is 34 days, with mutants living longer than double homozygous Smn1^tm1Msd and Tg(SMN2)89Ahmb control mice

• nearly 25% of mutants live beyond 40 days, with several living beyond P70

growth/size/body

decreased body size ( J:194969 )

• smaller size compared to wild-type controls at P12, although weight is greater than in double homozygous Smn1^tm1Msd and Tg(SMN2)89Ahmb control mice and some mutants eventually reach the weight of unaffected mice

behavior/neurological

behavior/neurological phenotype ( J:194969 )

N • mutants are more agile and generally fitter than double homozygous Smn1^tm1Msd and Tg(SMN2)89Ahmb control mice

impaired righting response ( J:194969 )

• 20-70% of mutants at P5-15 are able to right themselves compared to 100% of unaffected control mice (mice homozygous for Tg(SMN2)89Ahmb and heterozygous for Smn1^tm1Msd)

• starting at P5, mutants show increased ability to right compared to triple transgenics homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb (20-70% vs. 3-15% in the controls)

impaired coordination ( J:194969 )

• mutants stay on the rotorod for shorter periods of time than unaffected controls (mice homozygous for Tg(SMN2)89Ahmb and heterozygous for Smn1^tm1Msd)

decreased grip strength ( J:194969 )

• mutants show a slight decrease in grip strength compared to unaffected controls (mice homozygous for Tg(SMN2)89Ahmb and heterozygous for Smn1^tm1Msd)

muscle

decreased skeletal muscle fiber size ( J:194969 )

• skeletal muscle fibers are smaller than in wild-type controls, however they are larger than in triple transgenics homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

nervous system

abnormal neuromuscular synapse morphology ( J:194969 )

• mutants show an approximate 60% reduction of proprioceptive synapses onto motor neurons compared to triple transgenics homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

• P19 mutants show an increase in the percentage of neuromuscular junctions with perforated or fragmented endplates compared to controls homozygous for Tg(SMN2)89Ahmb, indicating a defect in synapse maturation

• mutants exhibit a modest but significant reduction in neuromuscular junction innervation in the longissimus muscle

cardiovascular system

thin interventricular septum ( J:194969 )

• mutants show a slight reduction in interventricular septum thickness, although this does not reach significance

• the interventricular septum thickness is significantly improved compared to triple transgenic controls homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

cardiac interstitial fibrosis ( J:194969 )

• mutants exhibit a modest, but significant increase in cardiac interstitial fibrosis compared to unaffected wild-type controls

• interstitial fibrosis is significantly improved when compared to triple transgenic controls homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

integument

epidermal necrosis ( J:194969 )

• mutants start to show signs of necrosis on the ears, tails, and/or eyes at approximately P40-P50

cellular

cardiac interstitial fibrosis ( J:194969 )

• mutants exhibit a modest, but significant increase in cardiac interstitial fibrosis compared to unaffected wild-type controls

• interstitial fibrosis is significantly improved when compared to triple transgenic controls homozygous for Smn1^tm1Msd and Tg(SMN2)89Ahmb and hemizygous for Tg(SMN2*delta7)4299Ahmb

epidermal necrosis ( J:194969 )

• mutants start to show signs of necrosis on the ears, tails, and/or eyes at approximately P40-P50

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:194969

Genotype
MGI:2677019

cx28

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB

mortality/aging

perinatal lethality, incomplete penetrance ( J:60592 )

• the majority of mice were stillborn or died within 6 hours of birth

• a slightly less than expected frequency of mice with this genotype suggests that some mice may be dying in utero

• in few cases, mice of this genotype survived up to 6 days of age

postnatal lethality, complete penetrance ( J:60592 )

• in few cases, mice of this genotype survived up to 6 days of age

behavior/neurological

abnormal suckling behavior ( J:60592 )

• mice that survived 4-6 days displayed a decrease or lack of suckling by 48 hours postnatal

tremors ( J:60592 )

• mice that survived 4-6 days showed a marked tremor within 72-96 hours postnatal

bradykinesia ( J:60592 )

• mice that survived 4-6 days showed a decrease in movement within 48-72 hours postnatal

muscle

muscle phenotype ( J:60592 )

N • no musculature atrophy was detected in the quadriceps or gastrocnemius of mice that survived 4-6 days

respiratory system

respiratory distress ( J:60592 )

• mice that survived 4-6 days displayed labored breathing by 48 hours postnatal

nervous system

motor neuron degeneration ( J:60592 )

• dramatic loss of motor neurons were observed in spinal cord (~35% loss) and facial nucleus(~40% loss) at postnatal day 5

• normal numbers of motor neurons were observed in spinal cord and facial nucleus in animals at postnatal day 1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:60592

Genotype
MGI:2677023

cx29

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2)566Ahmb/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB

limbs/digits/tail

short tail ( J:60592 )

• an unusual phenotype of these mice is a short thick tail, which is evident by ~ 2 weeks of age

thick tail ( J:60592 )

• an unusual phenotype of these mice is a short thick tail, which is evident by ~ 2 weeks of age

muscle

muscle phenotype ( J:60592 )

N • mice aged to 10 months failed to display any muscle weakness, loss of motor neurons, or other characteristics of spinal muscular atrophy

nervous system

nervous system phenotype ( J:60592 )

N • mice aged to 10 months failed to display any muscle weakness, loss of motor neurons, or other characteristics of spinal muscular atrophy

Genotype
MGI:2451057

cx30

• Allelic Composition: Gemin2^tm1Msd/Gemin2⁺; Smn1^tm1Msd/Smn1⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * MF1

nervous system

decreased motor neuron number ( J:81784 )

• number of lumbar motoneurons reduced by 34% at 5 months of age

• much less and non significant degeneration of facial motoneurons

Genotype
MGI:3775248

cx31

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(ACTA1-SMN)63Ahmb/Tg(ACTA1-SMN)63Ahmb; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:131663 )

• double mutants survive an average of 160 days, with some living up to a year

muscle

decreased skeletal muscle fiber size ( J:131663 )

• muscle fiber distribution is different from normal muscle; mice have a greater number of smaller diameter fibers relative to controls

limbs/digits/tail

tail necrosis ( J:131663 )

• tail becomes necrotic by 21 days of age, resulting in tail being very short

cellular

tail necrosis ( J:131663 )

• tail becomes necrotic by 21 days of age, resulting in tail being very short

Genotype
MGI:3847441

cx32

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*A111G)591Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:148541 )

N • mice survive over a year (some up to 1.5 years) compared to mutants not carrying the Tg(SMN2*A111G)591Ahmb transgene which have a median survival of 4.4-5 days

Genotype
MGI:3847443

cx33

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2*A111G)588Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:148541 )

N • no animals of this genotype are observed at birth

Genotype
MGI:3847444

cx34

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*)1951Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:148541 )

• animals have a mean lifespan of 6.5 days compared to spinal muscular atrophic (SMA) animals which do not carry the Tg(SMN2*)1951Ahmb transgene (4.4 day survival); Tg(SMN2*)1951Ahmb homozygosity does not significantly enhance survival

Genotype
MGI:3847565

cx35

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/0; Tg(SMN2*A111G)591Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:148541 )

• no animals of this genotype are observed at birth, indicating that the two missense SMN alleles cannot complement one another to form a functional complex and rescue the Smn1 deficiency

Genotype
MGI:3847566

cx36

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/0; Tg(SMN2*A111G)588Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:148541 )

• no animals of this genotype are observed at birth, indicating that the two missense SMN alleles cannot complement one another to form a functional complex and rescue the Smn1 deficiency

Genotype
MGI:3847439

cx37

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺; Tg(SMN2*A111G)591Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:148541 )

N • mice survive over a year (some up to 1.5 years) compared to mutants not carrying the Tg(SMN2*A111G)591Ahmb transgene which have a median survival of 4.4-5 days

Genotype
MGI:3847438

cx38

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN2*A111G)591Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

prenatal lethality, complete penetrance ( J:148541 )

• no animals of this genotype are observed at birth

Genotype
MGI:3775240

cx39

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(ACTA1-SMN)69Ahmb/Tg(ACTA1-SMN)69Ahmb; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:131663 )

• mice survive an average of 3.5 days, not significantly different from mean lifespan of 4.6 days of Smn1^tm1Msd homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:131663

Genotype
MGI:3775226

cx40

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(Prnp-SMN)92Ahmb/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:131663 )

• double mutants survive an average of 150 days

Genotype
MGI:3775225

cx41

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(Prnp-SMN)92Ahmb/Tg(Prnp-SMN)92Ahmb; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:131663 )

• double mutants survive an average of 210 days, with many living more than 1 year

• lifespan is less than that of Smn1^tm1Msd heterozygotes

muscle

decreased skeletal muscle fiber size ( J:131663 )

• muscle fiber distribution is different from normal muscle; mice have a greater number of smaller diameter fibers relative to controls

nervous system

nervous system phenotype ( J:131663 )

N • mice have normal motor neuron counts and lumbar root counts, compared to triple homozygotes for Smn1^tm1Msd, Tg(ACTA1-SMN)63Ahmb, and Tg(SMN2)89Ahmb

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:131663

Genotype
MGI:3663317

cx42

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/?
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

embryonic lethality, complete penetrance ( J:81238 )

• death occurs before E12

Genotype
MGI:3663316

cx43

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/Tg(SMN1*A2G)2023Ahmb; Grm7^{Tg(SMN2)89Ahmb}/?
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

nervous system

abnormal motor nerve collateral sprouting ( J:81238 )

• axon sprouting occurs in gastrocnemius and triceps muscles

• sprouts are both nodal and emerge from the neuromuscular junction (terminal)

• otherwise, phenotype is indistinguishable from littermates

Genotype
MGI:4835060

cx44

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

prenatal lethality, incomplete penetrance ( J:164444 )

• fewer than the expected numbers of mutants are seen at birth

cardiovascular system

thin interventricular septum ( J:164444 )

• reduction in width of the interventricular septum at E17.5

thin ventricular wall ( J:164444 )

• hearts have a thin and branched left ventricular wall at E17.5

Genotype
MGI:4835061

cx45

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

cardiovascular system

abnormal artery morphology ( J:164444 )

• thinner arterial wall

abnormal interventricular septum morphology ( J:164444 )

• the interventricular septum is partially flattened at P5 and P9

• the interventricular septum lacks the normal curvature which results in a D-shaped left ventricle

thin interventricular septum ( J:164444 )

• reduction in width of the interventricular septum at P5 and P9, but not at P2

increased heart left ventricle size ( J:164444 )

• enlargement of the left ventricle at P5 and P9

cardiac interstitial fibrosis ( J:164444 )

• interstitial fibrosis due to oxidative stress is initiated at P2 and progresses rapidly

decreased heart rate ( J:164444 )

prolonged RR interval ( J:164444 )

• electrocardiogram indicates longer R-R intervals

cellular

cardiac interstitial fibrosis ( J:164444 )

• interstitial fibrosis due to oxidative stress is initiated at P2 and progresses rapidly

oxidative stress ( J:164444 )

• marker analysis indicates oxidative stress in the heart

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:164444

Genotype
MGI:3847440

cx46

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}; Tg(SMN2*A111G)588Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:148541 )

N • mice survive over a year (some up to 1.5 years) compared to mutants not carrying the Tg(SMN2*A111G)588Ahmb transgene which show a survival of 4.4-5 days

N • animals have no obvious phenotype and are comparable to controls having normal mouse Smn

muscle

abnormal skeletal muscle morphology ( J:148541 )

• muscle morphology changes suggest muscles have undergone denervation followed by re-innervation

abnormal gastrocnemius morphology ( J:148541 )

• at 10 months, muscle fibers display hypertrophy with patches of atrophic fibers; average fiber size (mean size of 2870 um²) is greater than Tg(SMN2*A111G)588Ahmb/ Tg(SMN2*A111G)588Ahmb, Smn1^tm1Msd/ ⁺ (carrier) controls (mean size of 2456 um²) and fiber distribution is shifted to larger range of 2800-3900 um²

nervous system

nervous system phenotype ( J:148541 )

N • spinal cord have normal ventral root numbers relative to carrier controls

limbs/digits/tail

abnormal gastrocnemius morphology ( J:148541 )

• at 10 months, muscle fibers display hypertrophy with patches of atrophic fibers; average fiber size (mean size of 2870 um²) is greater than Tg(SMN2*A111G)588Ahmb/ Tg(SMN2*A111G)588Ahmb, Smn1^tm1Msd/ ⁺ (carrier) controls (mean size of 2456 um²) and fiber distribution is shifted to larger range of 2800-3900 um²

Genotype
MGI:3663312

cx47

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

premature death ( J:81238 )

• mean survival is 227 days

nervous system

abnormal motor neuron morphology ( J:81238 )

decreased motor neuron number ( J:81238 )

• 29% fewer lumbar spinal cord neurons than control in 3.5 month old mice

• 19% fewer facial nucleus neurons than control

• 5 day old mice did not exhibit reduced numbers of motor neurons

motor neuron degeneration ( J:81238 )

abnormal axon morphology ( J:81238 )

• ventral roots from L1-L5 lumbar spinal cord region contain few myelinated axons

• remaining axons are shriveled and exhibit Wallerian degeneration

abnormal neuromuscular synapse morphology ( J:81238 )

• increased number of neuromuscular junctions in gastrocnemius

neuronal intranuclear inclusions ( J:81238 )

• intranuclear aggregates (gems) of the SMN protein in spinal cord are fewer and less intense than in normal littermates

abnormal action potential ( J:81238 )

• reduced amplitudes in evoked muscle potentials from tibial nerve

abnormal motor nerve collateral sprouting ( J:81238 )

• axon sprouting occurs in gastrocnemius and triceps muscles

• sprouts are both nodal and emerge from the neuromuscular junction (terminal)

muscle

muscular atrophy ( J:81238 )

• angulated and atrophic fibers observed in gastrocnemius and to a lesser extent in quadriceps and intercostal muscles

abnormal muscle electrophysiology ( J:81238 )

• samples from multiple pelvic and thoracic muscles exhibit abnormal spontaneous activity of single muscle fibers and of motor units in 4-6 month old mice

• abnormal activity is occasionally accompanied by biphasic sharp waves

growth/size/body

decreased body size ( J:81238 )

• 20-40% smaller than normal littermates

weight loss ( J:81238 )

• toward the end of life

reproductive system

reduced fertility ( J:81238 )

behavior/neurological

poor grooming ( J:81238 )

• mice fail to groom efficiently toward the end of life

limb grasping ( J:81238 )

• muscle weakness exhibited by 3 weeks of age

decreased locomotor activity ( J:81238 )

• mice are less active by 3 weeks of age compared to normal littermates

• exhibit very little activity toward the end of life

respiratory system

hypopnea ( J:81238 )

• mice exhibit short, shallow breeding toward the end of life

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
juvenile spinal muscular atrophy		DOID:12376	OMIM:253400	J:81238

Genotype
MGI:3847437

cx48

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Grm7^{Tg(SMN2)89Ahmb}/Grm7⁺; Tg(SMN2*A111G)588Ahmb/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

mortality/aging ( J:148541 )

N • mice survive over a year in contrast to mutants without Tg(SMN2*A111G)588Ahmb which exhibit embryonic lethality

Genotype
MGI:3775243

cx49

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(SMN1*A2G)2023Ahmb/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

nervous system

decreased motor neuron number ( J:131663 )

• mice exhibit motor neuron loss

abnormal lumbar dorsal root ganglion morphology ( J:131663 )

• at 1 year of age, mice have significantly reduced root counts compared to mice homozygous for Smn1^tm1Msd, Tg(Prnp-SMN)92Ahmb, and Tg(SMN2)89Ahmb

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Werdnig-Hoffmann disease		DOID:13137	OMIM:253300	J:131663

Genotype
MGI:3775247

cx50

• Allelic Composition: Smn1^tm1Msd/Smn1^tm1Msd; Tg(ACTA1-SMN)63Ahmb/0; Grm7^{Tg(SMN2)89Ahmb}/Grm7^{Tg(SMN2)89Ahmb}
• Genetic Background: involves: 129P2/OlaHsd * FVB/N

mortality/aging

postnatal lethality, complete penetrance ( J:131663 )

• double mutants survive an average of 6.6 days, with some living past 15 days, representing a slight but significant increase compared to Smn1^tm1Msd homozygotes

Genotype
MGI:5286604

cx51

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor^{tm1.1(rtTA,EGFP)Nagy}; Smn1^tm1Msd/Smn1⁺; Tg(SMN2)#Ahmb/Tg(SMN2)#Ahmb; Tg(SMN2*delta7)4299Ahmb/Tg(SMN2*delta7)4299Ahmb; Tg(tetO-SMN2,-luc)#aAhmb/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA * FVB

mortality/aging

premature death ( J:174960 )

• only one mouse treated with doxycycline at P2 survived for 151 days

postnatal lethality, complete penetrance ( J:174960 )

• un-induced mice die on average at P14

• however, mice treated with doxycycline at E13 or at birth live for over 200 days

digestive/alimentary system

abnormal intestine morphology ( J:174960 )

• some doxycycline-treated mice exhibit impacted bowel and pockets of fluid and gas unlike control mice

growth/size/body

decreased body size ( J:174960 )

• doxcycline-treated mice are smaller than control mice

behavior/neurological

behavior/neurological phenotype ( J:174960 )

N • doxycycline-treated mice exhibit normal motor function

decreased locomotor activity ( J:174960 )

• in doxcycline-treated mice close to death

hearing/vestibular/ear

abnormal ear morphology ( J:174960 )

• some doxycycline-treated mice exhibit ear necrosis compared with control mice

nervous system

nervous system phenotype ( J:174960 )

N • doxycycline-treated mice exhibit normal endplates and miniature endplate currents and neuromuscular junctions